Endocrine disrupting effects of zearalenone, alpha- and beta-zearalenol at the level of nuclear receptor binding and steroidogenesis.

摘要

The mycotoxin zearalenone (ZEN) is a secondary metabolite of fungi which is produced by certain species of the genus Fusarium and can occur in cereals and other plant products. Reporter gene assays incorporating natural steroid receptors and the H295R steroidogenesis assay have been implemented to assess the endocrine disrupting activity of ZEN and its metabolites alpha-zearalenol (alpha-ZOL) and beta-zearalenol (beta-ZOL). alpha-ZOL exhibited the strongest estrogenic potency (EC(50) 0.022+/-0.001 nM), slightly less potent than 17-beta estradiol (EC(50) 0.015+/-0.002 nM). ZEN was ~70 times less potent than alpha-ZOL and twice as potent as beta-ZOL. Binding of progesterone to the progestagen receptor was shown to be synergistically increased in the presence of ZEN, alpha-ZOL or beta-ZOL. ZEN, alpha-ZOL or beta-ZOL increased production of progesterone, estradiol, testosterone and cortisol hormones in the H295R steroidogenesis assay, with peak productions at 10 muM. At 100 muM, cell viability decreased and levels of hormones were significantly reduced except for progesterone. beta-ZOL increased estradiol concentrations more than alpha-ZOL or ZEN, with a maximum effect at 10 muM, with beta-ZOL (562+/-59 pg/ml)>alpha-ZOL (494+/-60 pg/ml)>ZEN (375+/-43 pg/ml). The results indicate that ZEN and its metabolites can act as potential endocrine disruptors at the level of nuclear receptor signalling and by altering hormone production.